20-45891154-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_080749.4(NEURL2):c.-163T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,005,012 control chromosomes in the GnomAD database, including 381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (118 hom., cov: 33)
  • Exomes 𝑓: 0.011 (263 hom.)
• Consequence: NEURL2 NM_080749.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.655

Genes affected

NEURL2 (HGNC:16156): (neuralized E3 ubiquitin protein ligase 2) This gene encodes a protein that is involved in the regulation of myofibril organization. This protein is likely the adaptor component of the E3 ubiquitin ligase complex in striated muscle, and it regulates the ubiquitin-mediated degradation of beta-catenin during myogenesis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jun 2013]

CTSA (HGNC:9251): (cathepsin A) This gene encodes a member of the peptidase S10 family of serine carboxypeptidases. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate two chains that comprise the heterodimeric active enzyme. This enzyme possesses deamidase, esterase and carboxypeptidase activities and acts as a scaffold in the lysosomal multienzyme complex. Mutations in this gene are associated with galactosialidosis. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 20-45891154-A-C is Benign according to our data. Variant chr20-45891154-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 338520.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0984 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEURL2	NM_080749.4	c.-163T>G		5_prime_UTR_variant	1/2	ENST00000372518.5
NEURL2	NM_001278535.2	c.-163T>G		5_prime_UTR_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEURL2	ENST00000372518.5	c.-163T>G		5_prime_UTR_variant	1/2	1	NM_080749.4	P1

Frequencies

GnomAD3 genomes AF: 0.0164 AC: 2488 AN: 151984 Hom.: 117 Cov.: 33

Gnomad AFR AF: 0.00488

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00726

Gnomad FIN AF: 0.000566

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00864

Gnomad OTH AF: 0.0191

GnomAD4 exome AF: 0.0108 AC: 9208 AN: 852912 Hom.: 263 Cov.: 11 AF XY: 0.0106 AC XY: 4550 AN XY: 429186

Gnomad4 AFR exome AF: 0.00342

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.00589

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0104

Gnomad4 FIN exome AF: 0.00117

Gnomad4 NFE exome AF: 0.00782

Gnomad4 OTH exome AF: 0.0129

GnomAD4 genome AF: 0.0164 AC: 2488 AN: 152100 Hom.: 118 Cov.: 33 AF XY: 0.0179 AC XY: 1333 AN XY: 74344

Gnomad4 AFR AF: 0.00487

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00706

Gnomad4 FIN AF: 0.000566

Gnomad4 NFE AF: 0.00864

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.00200 Hom.: 0

Bravo AF: 0.0222

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Combined deficiency of sialidase AND beta galactosidase Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	7.4
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs184484066; hg19: chr20-44519793;